Biomedical subjects

J J Hostynek

Publications and source records attributed to J J Hostynek.

11 recordsLinked to original sources

PubMed2003

Factors determining percutaneous metal absorption.

Metals play a vital role in human, animal and plant physiology, and important research, past and ongoing, is directed towards exploring the interrelated mechanisms that govern their penetration through skin. Much insight has been gained through these efforts, but our understanding of the process is still incomplete, mainly due to the failure to allow for the effects of chemical speciation of metallic elements, especially the transition metals. Also, the skin as target organ presents imponderable and wide margins of variability. In vivo permeability is subject to homeostasis regulating the overall organism; in vitro, the sections of skin used for diffusion experiments are likely to present artifacts. Endeavors to define rules governing skin penetration to give predictive quantitative structure-diffusion relationships for metallic elements for risk assessment purposes have been unsuccessful, and penetration of the skin still needs to be determined separately for each metal species, either by in vitro or in vivo assays. Phenomena observed by us and other investigators, which appear to determine the process of skin permeation for a number of metals, are reviewed, separating the exogenous factors from the characteristics of the skin or other endogenous factors.

Age Factors↗

PubMed2003

Provocative use test of nickel coins in nickel-sensitized subjects and controls.

BACKGROUND: Consensus exists on levels of nickel release that are well tolerated in exposure to nickel-containing items in direct and continuous contact with skin (e.g. watches). The clinical relevance of nickel-containing coins eliciting nickel dermatitis associated with extensive occupational exposure (e.g. coins handled by cashiers) has not been determined. OBJECTIVES: To examine whether nickel-containing coins might be an elicitor of allergic contact dermatitis (ACD) in occupational settings with extensive exposure to coins (i.e. cashiers). METHODS: Eighteen subjects (10 nickel sensitized and eight non-nickel sensitized) completed this study after screening of history, physical examination and diagnostic patch testing (5% nickel sulphate). Each volunteer handled 10 coins (nickel-containing coins or non-nickel-containing coins) in a cross-over design at 5-min intervals (5 min handling followed by 5 min rest) for 8 h per day, for a total of 12 days excluding the weekend. One hand was gloved while the other was not during coin handling. Visual scoring and bioengineering measurements were recorded at each of four predetermined sites at baseline (day 1), end of day 5 and day 12 (last day of exposure). RESULTS: There were no statistical differences for either visual or bioengineering data comparing: (i) nickel-sensitized vs. non-nickel-sensitized subjects handling nickel-containing coins at day 1, day 5 and day 12; (ii) day 12 vs. day 1 (baseline) for nickel-sensitized subjects handling nickel-containing coins; (iii) handling of nickel-containing coins vs. non-nickel-containing coins by nickel-sensitized subjects at day 5 and day 12; (iv) gloved hand vs. ungloved hand of nickel-sensitized subjects handling nickel-containing coins at day 12. Limitations of the method and clinical extrapolation are detailed. CONCLUSIONS: Individuals handling these nickel-containing coins daily did not develop ACD, as judged by visual signs or bioengineering parameters.

Adult↗

PubMed2000

Use tests: ROAT (repeated open application test)/PUT (provocative use test): an overview.

As one step in defining the clinical relevance of exposure to an allergen identified with patch testing, use tests (provocative use test (PUT), and repeated open application test (ROAT)) have been used. In 1/2 of the cases of seemingly reliable patch tests, use tests are negative, suggesting that the patient's biologic threshold of response had not been reached with open application dosing. Dramatic differences exist in regional skin reactivity and percutaneous penetration. Negative results of use tests on normal skin may become positive on diseased skin. To refine this assay further, more controlled observations and analysis of reaction differences between normal and damaged skin, and among regional anatomic sites might be performed. In addition, we require a standardized measurement for the results. Use testing has significant potential in refinement of the evidence-based diagnosis of clinical relevance. However, for general validation, we should fill the deficiencies described above.

Animals↗

PubMed1993

Uptake of two zwitterionic surfactants into human skin in vivo.

To evaluate the potential risk associated with dermal exposure to nitrogen-containing amphiphiles commonly found in household and personal-care products, the uptake of N,N-dimethyl-N-dodecylglycine (dodecylbetaine, C12BET) and N,N-dimethyl-N-hexadecylglycine (hexadecylbetaine, C16BET) into human skin in vivo has been measured. The 14C-radiolabeled chemicals were applied in aqueous solution (C12BET concentrations 16, 100, and 800 mM; C16BET concentrations 0.14, 1.0, and 5.4 mM) to the dorsal upper arms of male volunteers for 30 min. At the end of this exposure period, the remaining applied solution was removed, the skin surface was thoroughly washed, and the stratum corneum at the administration site was removed by repeated tape-stripping. Dermal uptake was assessed (i) by direct measurement of the radioactivity recovered on the tape-strips, and (ii) from a predictive relationship previously derived from other research using a similar protocol. As expected, agreement between the two approaches was reasonable (generally within a factor of 3-4); the predictive relationship attempts to account for penetrant which cannot be recovered by the tape-stripping process, and anticipates, therefore, greater chemical exposure to the body than that expected on the basis of the tape-strip associated material alone. A positive control, using the previously studied penetrant, caffeine, demonstrated that the experimental procedure was conducted appropriately. Absorption of the betaines into human skin was significant (for C12BET, uptake was 28-160 nmol/cm2; that for C16BET was 2.3-19.5 nmol/cm2) and was primarily localized (as was caffeine) in the outer layers of the stratum corneum. In parallel experiments, in which unlabeled betaines were applied for 30 min, instead of tape-stripping, skin barrier function (measured by transepidermal water loss) was assessed. No betaine-induced effects on the stratum corneum were observed (in contrast to the sometimes large perturbations seen in vitro following considerably longer exposure times). Overall, the results indicated that the use of these betaines in personal care products, when intended for limited use and rinse-off application, gives no reason for safety concerns.

Adult↗

PubMed1991

The effects of zwitterionic surfactants on skin barrier function.

The action of five zwitterionic surfactants on the barrier function of hairless mouse skin has been studied in vitro. The surfactants considered were dodecylbetaine and hexadecylbetaine (C12BET and C16BET, respectively), hexadecylsulfobetaine (C16SUB), N,N-dimethyl-N-dodecylamine oxide (C12AO), and dodecyltrimethylammonium bromide (C12TAB). Excised skin was pretreated with each surfactant, at various concentrations, for 16 hr, following which the permeation of a model compound, nicotinamide, was measured. The action of the surfactants was assessed by comparing nicotinamide flux through surfactant-pretreated skin with that across control membranes which were exposed to buffer alone for 16 hr. All surfactants decreased skin barrier function to some extent. The degree of nicotinamide penetration enhancement induced was correlated with the ratio of the surfactant pretreatment concentration to the surfactant critical micelle concentration, suggesting that solubilization of stratum corneum lipids may be an important mechanism in explaining the effects observed. More detailed studies with 14C-radiolabeled C12BET and C16BET showed that the dodecyl analog was itself well absorbed, whereas the C16 compound partitioned into the skin favorably but then transferred only very slowly into the receptor phase. These observations were consistent with toxicity studies (albeit at much higher concentrations in a different animal model, the rat) which indicated that the dermal LD50 of C12BET was significantly less than that of C16BET (the value for which was so large that it could not be reliably determined). Overall, this study provides, we believe, useful information pertinent to the potential dermal toxicity of the surfactants considered following occupational or environmental exposure.

Administration, Oral↗

PubMed1990

Antiproliferative effects of amphiphilic molecules.

Previous investigations indicated that certain long chain amphiphiles possess immunosuppressive activity. Here we tested this concept by studying the ability of a series of nitrogen-containing amphiphiles of varying hydrocarbon chain lengths to inhibit the human mixed lymphocyte reaction (MLR). Seventeen of 29 compounds were classified as inhibitory in the MLR but not toxic to the cells, six were both inhibitory and toxic to the cells, and six were inactive at the concentrations tested. In contrast, cyclosporin A inhibited the MLR and was not toxic. With the hypothesis that the amphiphiles might act to inhibit cell proliferation in a nonspecific manner, they were tested on a battery of tumor cell lines at concentrations that did not show toxicity in the MLR. Whereas cyclosporin A did not inhibit the proliferation of tumor cells, most of the active amphiphiles did inhibit tumor cell proliferation and, in addition, killed the tumor cells. These results suggest that the amphiphiles are antiproliferative and do not show specificity of action on cells of the immune system. Finally, based on available data that showed poor skin penetration, no significant human health risk seems likely from skin contact with these chemicals, as they are currently used in household products or rinse-off personal care products.

Adult↗

PubMed1990

Irritation factors of sodium hypochlorite solutions in human skin.

The recommended concentration for patch testing with sodium hypochlorite [NaOCl] (bleach) is 1%, generally obtained by diluting commercial bleach. In doing so, other active (potentially irritant) components of bleach, especially hypochlorous acid [HOCl] and sodium hydroxide [NaOH], are neglected. Magnitudes of potential irritant species other than NaOCl, such as alkalinity, are ordinarily not labeled on the product, though they may vary considerably between brands. Thus, patch testing with 1% hypochlorite obtained by diluting different brand bleaches can potentially elicit non-specific irritant responses, also depending upon the test volume applied. In this study, skin irritation induced by 24-h patch testing with 20 microliters or 100 microliters, with constant NaOCl concentration (1%) and different NaOH concentrations (0.01-1.0%), was studied in adult human volunteers, by means of visual scores and skin color reflectance measurements. No irritation was elicited by application of 20 microliters 1% OCl-, independent of the NaOH concentration. However, all solutions induced significant irritation in a volume of 100 microliters. Skin reactions did not show a straight pH dose response, a maximum reaction being seen to the solution containing 0.1% NaOH. Skin surface pH values had increased when monitored immediately after removal of the patch material. However, 24 h later, baseline values were again reached at most sites, demonstrating an efficient buffering capacity of human skin, even after challenge with alkaline solutions of pH 13.4. We suggest that a non-irritant concentration for diagnostic patch testing for allergic contact dermatitis with an aluminum chamber, using 17 microliters to 20 microliters test volume, could be as high as 1% NaOCl and 1% NaOH.

Adult↗

PubMed1989

Hypochlorite sensitivity in man.

Observation of an individual with immediate-type reaction following exaggerated dermal exposure to hypochlorite-containing cleaning products prompted review of similar hypersensitivity reactions attributed to hypochlorite or other highly reactive chemicals. This review confirms isolated incidences of hypochlorite sensitivity of the delayed type (allergic contact dermatitis), as well as immediate-type reactions from inhalation or topical challenge of sensitized individuals. We conclude that it is possible that excessive and prolonged exposure to hypochlorite may in some cases result in irritation and damage to the skin. This potentially gives rise to altered proteins which in rare cases may cause hypersensitivity. This reaction is common to other reactive small molecules with a strong irritant action.

Adult↗

PubMed1988

Chromium in US household bleach.

Spectrophotometric analysis for chromium in hypochlorite bleach sampled at random throughout the USA shows that the highest level found in those products is of the order of 0.1 ppm (2/20). This probably does not represent a significant risk factor for chromate sensitization of the consumer population.

Chromium↗

PubMed1987

Percutaneous absorption, metabolism, and hemolytic activity of n-butoxyethanol.

A series of studies was conducted to examine the percutaneous absorption, distribution, excretion, and hemolytic activity of n-butoxyethanol (BE). Rats receiving a subcutaneous dose of 14C-labeled BE excreted the radioactivity in the urine (79%), expired air (10%), and feces (0.5%) within 72 hr. Of the organs analyzed, thymus and spleen showed elevated specific radioactivities as compared with blood. A percutaneous application of BE on rats, under nonocclusive conditions, showed 25-29% absorption within 48 hr. Peak blood levels of BE occurred at 2 hr after application; butoxyacetic acid (BAA) was found to be the major metabolite. Comparison of in vitro skin penetration data showed the following absorption pattern of BE: hairless rat much greater than pig greater than human skin. Hemolysis and associated hematological changes were noted in the rats which received single dermal applications of 260-500 mg/kg of BE. In vitro, BAA showed markedly greater hemolytic ability on rat erythrocytes than did BE. Human erythrocytes showed no hemolysis when incubated with BE or BAA at concentrations that are hemolytic to rat erythrocytes. An intravenous dose of 62.5 mg/kg of BE does not result in hemolysis or hemoglobinuria in the rat. The rat may be an animal model with increased susceptibility to the effects of BE compared with humans because of its rapid percutaneous absorptive ability and its greater hemolytic sensitivity.

Administration, Topical↗

PubMedDate not supplied

A quantitative structure-toxicity relationships model for the dermal sensitization guinea pig maximization assay.

We have developed quantitative structure-toxicity relationship (QSTR) models for assessing dermal sensitization using guinea pig maximization test (GPMT) results. The models are derived from 315 carefully evaluated chemicals. There are two models, one for aromatics (excluding one-benzene-ring compounds), and the other for aliphatics and one-benzene-ring compounds. For sensitizers, the models can resolve whether they are weak/moderate or severe sensitizers. The statistical methodology, based on linear discriminant analysis, incorporates an optimum prediction space (OPS) algorithm. This algorithm ensures that the QSTR model will be used only to make predictions on query structures which fall within its domain. Calculation of the similarities between a query structure and the database compounds from which the applicable model was developed are used to validate each skin sensitization assessment. The cross-validated specificity of the equations ranges between 81 and 91%, and the sensitivity between 85 and 95%. For an independent test set, specificity is 79%, and sensitivity 82%.

Administration, Topical↗